Reference measurement procedure for CSF amyloid beta (Aβ)1–42 and the CSF Aβ1–42/Aβ1–40 ratio – a cross-validation study against amyloid PET
Pannee, Josef ; Portelius, Erik ; Minthon, Lennart LU ; Gobom, Johan ; Andreasson, Ulf ; Zetterberg, Henrik LU ; Hansson, Oskar LU
and Blennow, Kaj
LU
(2016)
In Journal of Neurochemistry
139(4).
p.651-658
- Abstract
A clinical diagnosis of Alzheimer's disease is currently made on the basis of results from cognitive tests in combination with medical history and general clinical evaluation, but the peptide amyloid-beta (Aβ) in cerebrospinal fluid (CSF) is increasingly used as a biomarker for amyloid pathology in clinical trials and in recently proposed revised clinical criteria for Alzheimer's disease. Recent analytical developments have resulted in mass spectrometry (MS) reference measurement procedures for absolute quantification of Aβ1–42 in CSF. The CSF Aβ1–42/Aβ1–40 ratio has been suggested to improve the detection of cerebral amyloid deposition, by compensating for inter-individual variations in total Aβ... (More)
A clinical diagnosis of Alzheimer's disease is currently made on the basis of results from cognitive tests in combination with medical history and general clinical evaluation, but the peptide amyloid-beta (Aβ) in cerebrospinal fluid (CSF) is increasingly used as a biomarker for amyloid pathology in clinical trials and in recently proposed revised clinical criteria for Alzheimer's disease. Recent analytical developments have resulted in mass spectrometry (MS) reference measurement procedures for absolute quantification of Aβ1–42 in CSF. The CSF Aβ1–42/Aβ1–40 ratio has been suggested to improve the detection of cerebral amyloid deposition, by compensating for inter-individual variations in total Aβ production. Our aim was to cross-validate the reference measurement procedure as well as the Aβ1–42/Aβ1–40 and Aβ1–42/Aβ1–38 ratios in CSF, measured by high-resolution MS, with the cortical level of Aβ fibrils as measured by amyloid (18F-flutemetamol) positron emission tomography (PET). We included 100 non-demented patients with cognitive symptoms from the Swedish BioFINDER study, all of whom had undergone both lumbar puncture and 18F-flutemetamol PET. Comparing CSF Aβ1–42 concentrations with 18F-flutemetamol PET showed high concordance with an area under the receiver operating characteristic curve of 0.85 and a sensitivity and specificity of 82% and 81%, respectively. The ratio of Aβ1–42/Aβ1–40 or Aβ1–42/Aβ1–38 significantly improved concordance with an area under the receiver operating characteristic curve of 0.95 and a sensitivity and specificity of 96% and 91%, respectively. These results show that the CSF Aβ1–42/Aβ1–40 and Aβ1–42/Aβ1–38 ratios using the described MS method are strongly associated with cortical Aβ fibrils measured by 18F-flutemetamol PET. (Figure presented.).
(Less)
- author
- Pannee, Josef
; Portelius, Erik
; Minthon, Lennart
LU
; Gobom, Johan
; Andreasson, Ulf
; Zetterberg, Henrik
LU
; Hansson, Oskar
LU
and Blennow, Kaj
LU
- organization
- publishing date
- 2016-11-01
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Alzheimer's disease, amyloid beta-peptides, cerebrospinal fluid, mass spectrometry, positron-emission tomography
- in
- Journal of Neurochemistry
- volume
- 139
- issue
- 4
- pages
- 8 pages
- publisher
- Wiley-Blackwell
- external identifiers
-
- scopus:84990037151
- pmid:27579672
- wos:000387842800012
- ISSN
- 0022-3042
- DOI
- 10.1111/jnc.13838
- language
- English
- LU publication?
- yes
- id
- 7f8c53f6-005e-4015-a115-4ef76ee155ff
- date added to LUP
- 2016-12-05 12:03:50
- date last changed
- 2024-05-04 14:38:02
@article{7f8c53f6-005e-4015-a115-4ef76ee155ff,
abstract = {{<p>A clinical diagnosis of Alzheimer's disease is currently made on the basis of results from cognitive tests in combination with medical history and general clinical evaluation, but the peptide amyloid-beta (Aβ) in cerebrospinal fluid (CSF) is increasingly used as a biomarker for amyloid pathology in clinical trials and in recently proposed revised clinical criteria for Alzheimer's disease. Recent analytical developments have resulted in mass spectrometry (MS) reference measurement procedures for absolute quantification of Aβ<sub>1–42</sub> in CSF. The CSF Aβ<sub>1–42</sub>/Aβ<sub>1–40</sub> ratio has been suggested to improve the detection of cerebral amyloid deposition, by compensating for inter-individual variations in total Aβ production. Our aim was to cross-validate the reference measurement procedure as well as the Aβ<sub>1–42</sub>/Aβ<sub>1–40</sub> and Aβ<sub>1–42</sub>/Aβ<sub>1–38</sub> ratios in CSF, measured by high-resolution MS, with the cortical level of Aβ fibrils as measured by amyloid (<sup>18</sup>F-flutemetamol) positron emission tomography (PET). We included 100 non-demented patients with cognitive symptoms from the Swedish BioFINDER study, all of whom had undergone both lumbar puncture and <sup>18</sup>F-flutemetamol PET. Comparing CSF Aβ<sub>1–42</sub> concentrations with <sup>18</sup>F-flutemetamol PET showed high concordance with an area under the receiver operating characteristic curve of 0.85 and a sensitivity and specificity of 82% and 81%, respectively. The ratio of Aβ<sub>1–42</sub>/Aβ<sub>1–40</sub> or Aβ<sub>1–42</sub>/Aβ<sub>1–38</sub> significantly improved concordance with an area under the receiver operating characteristic curve of 0.95 and a sensitivity and specificity of 96% and 91%, respectively. These results show that the CSF Aβ<sub>1–42</sub>/Aβ<sub>1–40</sub> and Aβ<sub>1–42</sub>/Aβ<sub>1–38</sub> ratios using the described MS method are strongly associated with cortical Aβ fibrils measured by <sup>18</sup>F-flutemetamol PET. (Figure presented.).</p>}},
author = {{Pannee, Josef and Portelius, Erik and Minthon, Lennart and Gobom, Johan and Andreasson, Ulf and Zetterberg, Henrik and Hansson, Oskar and Blennow, Kaj}},
issn = {{0022-3042}},
keywords = {{Alzheimer's disease; amyloid beta-peptides; cerebrospinal fluid; mass spectrometry; positron-emission tomography}},
language = {{eng}},
month = {{11}},
number = {{4}},
pages = {{651--658}},
publisher = {{Wiley-Blackwell}},
series = {{Journal of Neurochemistry}},
title = {{Reference measurement procedure for CSF amyloid beta (Aβ)<sub>1–42</sub> and the CSF Aβ<sub>1–42</sub>/Aβ<sub>1–40</sub> ratio – a cross-validation study against amyloid PET}},
url = {{http://dx.doi.org/10.1111/jnc.13838}},
doi = {{10.1111/jnc.13838}},
volume = {{139}},
year = {{2016}},
}